I was given a subscription to Wired magazine as a holiday
gift and the first issue I received, December 09, had a fascinating
health care story to report. It details the work of Dr. David Eddy and his team
who have developed a complex computer program to simulate controlled clinical
trials. That phrase does not do justice to the program which is apparently, in
the minds of some, nothing short of spectacular. There are of course many
naysayers who are quoted but I dont have enough knowledge about the
issues raised to have an opinion either way.
What I do know, and what I want to reiterate from a previous blog, is
that we must all be careful about accepting without question the results of
randomized, double-blind, placebo-controlled clinical trials (RCTs). RCTs
provide some of the best clinical and therapeutic data available but their cost
and time constraints limit the extent to which the data can be directly applied
to the patient in your office right now.
In order to obtain the most definitive data in the shortest possible
time, patients enrolled in many RCTs, particularly those evaluating a potential
new therapy, are carefully screened such that as many potentially confounding
variables as possible are excluded from the study. This is a must for these
RCTs, otherwise they would almost certainly require more patients studied over
longer periods to have sufficient data to correctly document that the therapy
does or does not work as anticipated from the many years of research that
precedes these RCTs.
To remove the study population one step further away from the patient in
front of you, an experienced team of clinical trial monitors and clinical trial
nurses are on hand to ensure that compliance with the therapy in question is
optimized, as is compliance with turning up for all serial lab studies. In the
real world of health care, how many of us have the time or manpower to
Next is the issue with coexistent conditions, with most trials excluding
potential study subjects in whom a coexisting condition may put them at
increased risk of an adverse event no matter how effective the therapy being
evaluated might be. A critical determinant in patient eligibility is the
ongoing use of nonstudy medications that may or may not affect the outcome of
the clinical trial.
In summary, the most efficient and cost-effective way to conduct an RCT
is to have the study groups, both placebo and active drug, as free of
potentially confounding issues as possible.
How often does that happen in day-to-day clinical practice? Not very in
my experience, particularly with respect to poly-pharmacy. Yet we dont
have too many options! Patients with diabetes, for example, are very likely to
have a requirement for therapies to control blood pressure and dyslipidemia,
not to mention renal, vascular and neurologic complications and associated
therapy. Add obesity and associated degenerative joint disease and
poly-pharmacy is rampant. It is unclear what proportion of patients with
osteoporosis has a secondary cause of bone loss with active treatment, but it
is not a trivial number.
None of the above is new so where is this leading to?
There is appropriate increasing awareness of the need to practice
preventive medicine but I am concerned about the potential long-term effects of
prevention programs that rely on medication. In the field of endocrinology
alone there is a trend to lower the threshold where pharmacologic intervention
is recommended hypothyroidism, pre-diabetes, lipids, blood pressure, and
of course osteopenia.
I know my bias is showing but I want to plug
FRAX- the new tool in the
osteoporosis field - that provides a 10-year probability of fracture risk
in an individual patient. Two women with the same spine and/or hip bone density
are likely to have different fracture risks that are dependent on factors other
than BMD. If we could provide similar numerical information regarding risk of
heart attack, stroke, peripheral vascular disease, etc. perhaps, and only
perhaps, we could be more circumspect about poly-pharmacy.
A woman whose father suffered a stroke at age 76 but whose mother died
peacefully at age 93 without ever having had a fragility fracture is likely to
be more concerned about her BP and lipid profile than her BMD no matter how low
it may be. With tools like this available to us, we are likely to be more
circumspect about poly-pharmacy. Just imagine what that might do to compliance
I have enough trouble typing with two fingers at a time so I know better
than to even think about looking further into Dr. Eddys
Archimedes programs. Lets hear from our more technological